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Gene therapy using adenovirus against malignant mesothelioma
Akinobu Gotoh1, Takeshi Kanno, Hisao Nagaya
1Laboratory of Cell and Gene Therapy Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
Background:
Adenovirus vectors have been utilized for cancer gene therapies. The present study examined the oncolytic effects of adenovirus type 5 (Ad5) and fiber-substituted conditionally replicating adenovirus (CRAD) Ad5/F35 vectors on the human malignant mesothelioma cells MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells.
Materials And Method:
For the adenovirus, the first mRNA/protein to be made (~1 h after infection) is E1A. Ad5F35 and Ad5 CRAD vectors containing the E1 gene controlled by the human midkine promoter (Ad5F35/MKp-E1 and Ad5/MKp-E1, respectively) were constructed. Western blotting and cell viability assays were carried out in cells transfected with Ad5/MKp-E1 and Ad5F35/MKp-E1.
Results:
Coxsackie and adenovirus receptor (CAR), a cell surface target of Ad5, and CD46, a cell surface target of Ad35, were expressed in all the malignant mesothelioma cell lines examined here, as much as in HEK293 cells, with no significant differences in the expression levels among cells. Both Ad5/MKp-E1 and Ad5F35/MKp-E1 induced oncolysis of malignant mesothelioma cells in a viral particle-dependent manner, with similar efficacy.
Conclusion:
The results of the present study suggest that both Ad5/MKp-E1 and Ad5F35/MKp-E1 are useful for the gene therapy of human malignant mesothelioma.
Insights
Adenovirus vectors show promise for mesothelioma gene therapy. Both Ad5/MKp-E1 and Ad5F35/MKp-E1 demonstrated similar efficacy in inducing oncolysis of malignant mesothelioma cells.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Mesothelioma research
Background:
- Adenovirus type 5 (Ad5) and fiber-substituted conditionally replicating adenovirus (CRAD) Ad5/F35 vectors are explored for cancer gene therapies.
- Malignant mesothelioma cell lines (MSTO-211H, NCI-H28, NCI-H2052, NCI-H2452) were used to evaluate oncolytic effects.
Purpose of the Study:
- To assess the oncolytic efficacy of Ad5 and Ad5/F35 CRAD vectors in human malignant mesothelioma cells.
- To investigate the potential of engineered adenovirus vectors for mesothelioma gene therapy.
Main Methods:
- Construction of Ad5F35 and Ad5 CRAD vectors (Ad5F35/MKp-E1 and Ad5/MKp-E1) with the E1 gene under the human midkine promoter.
- Evaluation of viral effects using Western blotting and cell viability assays in transfected mesothelioma cells.
Main Results:
- All examined mesothelioma cell lines expressed both Coxsackie and adenovirus receptor (CAR) and CD46, targets for Ad5 and Ad35, respectively.
- Both Ad5/MKp-E1 and Ad5F35/MKp-E1 induced significant oncolysis in malignant mesothelioma cells in a dose-dependent manner with comparable efficacy.
Conclusions:
- Engineered adenovirus vectors Ad5/MKp-E1 and Ad5F35/MKp-E1 show potential as therapeutic agents for human malignant mesothelioma.
- These vectors represent a promising strategy for gene therapy in malignant mesothelioma treatment.
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